Biographical Memoirs Volume 88 (2006) / Chapter Skim
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Fritz Albert Lipmann
Fritz Albert Lipmann
Pages 246-267
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From page 247... ...
The Lipmann family regularly spent the summer there, close to the seashore. The taxis were droschkes, horse-drawn carriages.
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From page 248... ...
He enrolled in a remarkable three-month course in biochemistry that was taught by Peter Rona, who had worked with Leonor Michaelis. Rona taught three Nobel prizewinners: E.B.
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From page 249... ...
Other investigators in Meyerhof's laboratory included Karl Lohmann, who discovered Adenosine Triphosphate (ATP) , and Karl Meyer, Severo Ochoa , Dean Burk and David Nachmansohn.
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Lipmann showed that creatine phosphate was cleaved during muscle contraction, although he did not establish its role conclusively (1927)
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From page 251... ...
Lipmann described the people involved with the theatre as a "clan, closed up and agitated by their problems and intrigues." He noted that they included "unusual characters and beautiful women, often astonishingly intelligent, who were not unsimilar to scientists." He spent considerable time with painter Friedel Sebba, who had made a portrait of Lipmann and his brother Heinz in 1926. ENERGY Hill and Meyerhof had shown that there is a close relationship between the production of heat and the formation of lactic acid from glycolysis when muscles contract in the absence of oxygen.
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From page 252... ...
The move to Berlin had the added advantage that he could more easily meet Freda Hall. In Fischer's laboratory he developed a technique to measure the growth of cells in tissue culture by the manometric measurement of oxygen uptake by fibroblasts in Warburg vessels.
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From page 253... ...
Lipmann asked Levene if he could work on the phosphate link in phosphoproteins because he thought that there might be an energy-rich linkage to nitrogen as in creatine phosphate. Instead, he encountered O-esterified phosphate in vitellic acid, a protein purified from egg yolk.
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From page 254... ...
However, when isotopically labeled phosphate and adenylic acid were added to this preparation, the oxidation of pyruvate led to the production of ATP from ADP and phosphate. This is now known as oxidative phosphorylation, the primary source of readily usable energy in aerobic organisms.
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From page 255... ...
It was known that deuterium-labelled acetate was incorporated into fatty acids, steroids and amino acids, and Lipmann had shown that acetyl phosphate was formed from ATP and acetate in bacterial extracts. It was at this time that he wrote his famous paper "The metabolic generation and utilization of phosphate bond energy" (1941)
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From page 256... ...
The importance of his paper on activated phosphate compounds as a source of readily available energy was recognized quickly, and soon a number of biochemists came to work in his laboratory. He received financial support for his research from the Commonwealth Fund and was able to support a remarkably capable technician, Constance Tuttle, who worked with him for many years.
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From page 257... ...
Roger Williams, the discoverer of pantothenic acid, and Beverly Guinard hydrolysed the cofactor and showed that it contained â-alanine and adenylic acid in equivalent amounts. Lipmann's group then used alkaline phosphatase and an enzyme obtained from an extract of liver to cleave the compound and obtained pantothenic acid.
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From page 258... ...
that included descriptions of the role of acyl-CoA thioesters in the synthesis of fatty acids and steroids, as well as the acylation of arylamines and of acetyl-CoA itself, in acetoacetate synthesis. David Novelli, Nathan Kaplan and Mary Ellen Jones played especially important roles in the laboratory, as senior investigators who provided advice and help to others.
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From page 259... ...
However, Leonard Spector, then associated with Paul Zamecnik in a neighbouring laboratory, was able to perform the first effective synthesis of this material by analogy with the synthesis of acetyl phosphate by the reaction of inorganic phosphate with ketene. Carbamyl phosphate, generated by the reaction of potassium cyanate with inorganic phosphate, was thus identified as the material that Jones had isolated, and was then tested for activity in microbial and human preparations.
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From page 260... ...
The combination of cyanate with inorganic phosphate attracted Lipmann's attention as one of several reactions by which the first biological molecules could have been formed, leading to the spontaneous formation of a form of ~P, interconvertible with the anhydride bonds in ATP. However, he regarded polymeric anhydrides of phosphoric acid as more likely to have served as the primary phosphoryl donors in early organisms.
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From page 261... ...
Mahlon Hoagland, working in Zamecnik's laboratory, demonstrated the existence of amino-acid-activating enzymes in rat liver, and showed that the action of these enzymes resulted in cleavage of ATP to pyrophosphate, which was consistent with formation of aminoacid-AMP anhydrides similar to the anhydrides that had been shown by Paul Berg to be formed during acetate activation. Lipmann's laboratory became involved when Earl Davie and William Koningsberger isolated the tryptophan-activating enzyme and showed that it was specific for that amino acid.
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From page 262... ...
Through the use of puromycin, an antibiotic that resembles the terminal adenosine residue of tRNA and can participate in some of its reactions, Anne-Louise Haenni and Jean LucasLennard showed that GTP hydrolysis leads to translocation of peptidyl-tRNA from an acceptor site to a donor site, where it stands ready to transfer its peptide to the next incoming amino acyl-tRNA. These experiments defined the chemical steps in protein synthesis as they are understood today.
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From page 263... ...
Lipmann died on 24 July 1986, at the age of eighty-seven, not long after having learned that his latest research grant application had been successful.
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264 B I O G R A P H I C A L M E M O I R S R E F E R E N C E DeMeio.
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191:442. 1929 Weitere Versuche über den Mechanismus der Fluoridhemmung und die Dissoziationskurve des Fluor-Methämoglobins.
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From page 266... ...
Spector. Carbamyl phosphate, the car bamyl donor in enzymatic citrulline synthesis.
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